The endocrine role of the kidney as the producer of the calcigenic steroid hormone, 1,25-dihydroxyvitamin D3, is now well recognized. What is not well understood is the degree to which and the mechanisms by which this important metabolic step might be perturbed during disturbances of other endocrine systems. The frequent disturbances in calcium metabolism observed in clinical diabetes and the consistency with which intestinal calcium transport is reduced in experimental diabetes and restored by insulin, strongly suggest that insulin may interact with the calcium homeostasic system. The goal of the proposed research is to determine whether and how insulin influences the metabolism of the renal cell, with special emphasis on the role of this cell in supplying the potent steroid hormone, 1,25-dihydroxyvitamin D3. Primary cultures of chick kidney cells, which have already been shown to carry out this metabolic step and to be subject to regulation, will be the model system. The dependence of these cells on insulin on the metabolic capabilities of the cells will be investigated; these include glycolysis, gluconeogenesis and cyclic nucleotide metabolism. Of great interest will be the detailed study of whether insulin influences, at the level of the renal cell, the metabolism of 25-hydroxyvitamin D3 to its dihydroxylated products, 1,25- and 24,25-dihydroxy-vitamin D3. The results of these studies will increase the understanding of how and why calcium metabolism is perturbed by changes in insulin status and may lead to better understanding and management of patients with diabetes mellitus.